Evaluating the frequency of neurological symptoms in COVID‐19 patients: A cross‐sectional study

Abstract Background and Aims Due to the recent emergence of COVID‐19, the exact pathology of this disease has not been determined. Therefore, this study evaluated the frequency of neurological symptoms in patients with COVID‐19. Methods This cross‐sectional study was conducted on 2200 in patients with COVID‐19 who were selected from an educational hospital in Sanandaj, Iran, from April 2020 to March 2021. The research samples were selected by census, all patients with COVID‐19 were admitted to the hospital. The data collection tool was a checklist of the studied variables (dizziness, headache, and impaired consciousness) prepared by the researchers based on the specialists' opinions. The researcher completed these checklists based on the patients' hospitalization records. The data were analyzed by descriptive and analytical statistical tests using SPSS Software Version 20. The quantitative variables were compared using the independent t‐test. The χ 2 test was also used to compare qualitative variables. A p Value of less than 0.05 was considered statistically significant. Results The mean age of the patients was 57.41 years old, of whom 53.1% were male. The average blood oxygen level of the patients was 88.10%, and most disease symptoms were related to shortness of breath and cough, with a frequency of 24.3%. In addition, 20.8% of patients needed hospitalization in intensive care unit. The highest frequency of central and peripheral nervous system manifestations was related to headache, ageusia (loss of sense of taste), hyposmia (A decreased sense of smell and anosmia (The complete loss of smell). Finally, 15.3% of patients died, and 84.7% recovered. The analytical findings showed a significant relationship between the disease outcome and patients' dizziness, consciousness disorder, seizure and ageusia. There was a significant relationship between gender and headache in patients. There was a significant difference between the mean age and oxygen level with central and peripheral nervous system manifestations (dizziness, headache, impaired consciousness, smell disorder) and the disease outcome in patients. Conclusion The pathophysiology of COVID‐19 virus infection involving the central nervous system is not fully understood. Neurological symptoms of this virus include delirium, headache, decreased level of consciousness, and seizures. Identifying the symptoms and mechanisms of neurological complications of COVID‐19 is necessary for proper screening and complete treatment because a patient infected by COVID‐19 may not show respiratory failure signs but may be a carrier. A complete and accurate knowledge of the symptoms and complications of this infection for proper screening of patients to prevent transmission and spread of this disease is critically needed.

China, as the cause of pneumonia in people. [1][2][3][4] The disease caused by this virus was named COVID-19 by the World Health Organization, 5 spread throughout China and other countries, and became a critical health condition worldwide. The average incubation period of the SARS-CoV-2 virus is 3−7 days. 6,7 Coronaviruses are a large family of viruses, causing diseases from simple colds to severe health problems, such as Middle East Respiratory Syndrome (MERS-COV) and Severe Respiratory Syndrome (SARS). 5 COVID-19 is a new strain of this virus family, which was first introduced in China and never observed in human populations earlier before. 7,8 Different clinical symptoms have been reported for COVID-19, from asymptomatic to severe forms of the disease, leading to acute respiratory distress (ARDS) and requiring special care, mechanical ventilation, and multiple organ failure. 6 Common symptoms of this disease include fever, dizziness, fatigue, nasal congestion, and muscle pain. Standard tests include lymphopenia, high levels of C-reactive protein in plasma, and increased lactate dehydrogenase. About 7−10% of patients progress critically, and 1−2% die, even though these results vary by region. 9 This disease is transmitted by spreading tiny respiratory droplets of infected people or touching the face after hand contact with contaminated surfaces. Although most affected people initially have mild symptoms similar to a simple cold, more severe symptoms appear a few days after affecting. 10 These symptoms include a nonproductive cough, dizziness, sore throat, fever, shortness of breath, muscle pain, and loss of sense of smell. Gastrointestinal symptoms such as diarrhea, skin complications, and red eyes have also been observed in some patients. 11 Failure in the functioning of the central nervous system, heart, kidney, and liver is observed in some patients with COVID- 19. 12 Studies have shown that the COVID-19 virus can induce fever, nonproductive cough, shortness of breath, myalgia, fatigue, malaise, and gastrointestinal disturbances in affected patients. In more severe cases, infections cause viral pneumonia, severe ARDS, and even death. 13,14 In addition to respiratory failure and cardiac symptoms, this disease can also cause neurological symptoms in patients, including headaches, dizziness, ataxic encephalitis, stroke, and seizures affecting the central nervous system. 2,15 Neurological complications include demyelinating conditions after infection. 16 The most commonly reported symptoms include headache and dizziness, encephalopathy (abnormal brain function or brain structure), delirium, blurred vision, tinnitus (ringing in the ears) and fatigue. 4 The mentioned difficulties are cerebrovascular accidents such as cerebral ischemic stroke, intracerebral hemorrhages, and cerebral vasculitis. 2,11 The peripheral nervous system might also be affected. Ageusia, anosmia/ hyposmia, myalgia, paresthesia, encephalitis (inflammation of the active tissues of the brain) or encephalopathy and Guillain-Barré syndrome (A disorder in which your body's immune system attacks your nerves) are the most reported disorders affecting the peripheral nervous system in patients with 17,18 Given the limited studies regarding COVID-19 pathology and its pandemic in 2020, many of the disease symptoms are unknown and lack a definitive treatment. Therefore, this study investigated the neurological manifestations of COVID-19 patients treated at educational hospitals in Sanandaj, Iran, during the pandemic wave to understand the wide range of neurological symptom manifestations in their global occurrence.

| METHOD
This cross-sectional study was conducted on all COVID-19 patients hospitalized between April 2020 to March 2021. The sampling was performed by the census, and 2200 hospitalized patients were included in the study. The minimum required sample size was calculated using the online sample size calculator (the estimated COVID-19 prevalence of 33%, 19 type 1 error rate (α) of 0.05, and absolute error of precision (d) of 0.02); and it was found to be 2124 (https://riskcalc.org/samplesize/). To find the final adjusted sample size, allowing nonresponse rate of 10%, the adjusted sample size was 2336. The data of patients were collected by the researcher after obtaining permission from the ethics committee.
The files of hospitalized patients in medical records were used to collect information. The relevant units in the university and hospital were coordinated to obtain permission to access the patients' files. In addition, a picture archiving and communication system (PACS) was used to access CT scans of patients' brains.
Medical records were reviewed only after verbal consent was obtained from patients who had been discharged by the phone number listed in their records, and this consent was waived for patients who had died. All patients whose files have been

| INCLUSION AND EXCLUSION CRITERIA
The study's inclusion criteria were positive and hospitalized COVID-19 patients, and the exclusion criteria included an underlying neurological disease.

| DATA ANALYSIS METHOD
The data collected in this study were analyzed using SPSS software version 20 after the information was collected. The quantitative data were described using mean and SD, and the qualitative data were assessed by frequency and percentage.
Then, the quantitative variables were compared using the independent t-test. The χ 2 test was also used to compare qualitative variables. A p value of less than 0.05 was considered statistically significant.

| RESULTS
The mean age of the patients was 57.41 years old, of whom 53.1% were male. The average blood oxygen level of the patients was 88.10%, and most disease symptoms were related to shortness of breath and cough (24.3%). In addition, 20.8% of patients needed hospitalization in ICU. The highest frequency of central and peripheral nervous system manifestations was related to headache, ageusia, hyposmia and anosmia. In addition, 2.5% of the studied patients were visited by a neurologist. Finally, 15.3% of patients died, and 84.7% recovered (Tables 1-4). Table 5 presents the relationship between the disease outcome and manifesting the central nervous system. Chisquare analysis shows a statistically significant relationship between the disease outcome and dizziness, impaired consciousness, and seizures in the studied patients. A correlation is also shown between the disease outcome and the peripheral nervous system manifestations in the study patients. There is a significant relationship between the disease outcome and the Neuralgia and smell abnormalities in the studied patients. According to the study, gender is significantly related to headaches caused by central nervous system manifestations in patients. In addition, there is a significant relationship between the disease outcome and the peripheral nervous system and between gender and the peripheral nervous system. Table 6 demonstrates the correlation between disease outcome with age and blood oxygen level. The t-test shows a statistically significant correlation between the mean age and oxygen level and the disease outcome in the studied patients.
T A B L E 1 Average quantitative variables in the studied patients.  A total of 78 patients (36.4%) had neurological manifestations. The most common neurologic symptoms in severe COVID-19 patients were acute brain disease, impaired consciousness, and skeletal muscle symptoms. 24  Studies of the damage caused by COVID-19 on the respiratory system have shown that the efficiency of this system for the exchange of respiratory gases decreases, and the amount of oxygen in the blood decreases, which can lead to impaired brain function and a decrease in the level of consciousness and convulsions. 25,26 In addition, there is a significant relationship between the disease outcome and ageusia, hyposmia and anosmia in the studied patients.
The highest percentage of patients with these disorders improved, and only one died from a smell disorder. Ageusia, hyposmia and anosmia are the most common symptoms of the effect of COVID-19 on the nervous system in patients with COVID-19. 27 Unlike other systems, the nerve receptors of the olfactory system are located precisely on the nerve. When the virus can infect the receptor, the nerve can be infected with the virus, entering directly from this point and involving brain neurons. 28,29 T A B L E 6 Determining the relationship between the disease outcome with age and blood oxygen level.

ACKNOWLEDGMENTS
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data that support the finding of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

ETHICS STATEMENT
The